PROLONGED ENHANCEMENT OF PASSIVE-AVOIDANCE IN RATS BY A HYDANTOIN DERIVATIVE OF NALOXONE

Opiate antagonists prevent morphine analgesia and enhance training in laboratory animals. We have synthesized and tested a novel derivative of the opiate antagonist naloxone. This derivative, naloxyl-6-alpha-spirohydantoin, was longer acting than the parent compound against the effects of morphine in vivo and was significantly less toxic. We now report that the naloxyl-hydantoin derivative, administered prior to training in a dose of 2 mg/kg, was more effective than naloxone in enhancing acquisition of passive avoidance in young adult male rats. Furthermore, the passive avoidance syndrome was retained longer in animals treated with naloxyl-hydantoin than in those treated with naloxone itself. The new compound merits further evaluation as a long-acting antagonist of opiates and opioids and as a memory and/or alertness enhancing agent.